We will develop a new synthetic methodology where high yielding photochemical key reactions are incorporated into a diversity-oriented split-and-pool combinatorial synthesis. Photochemical reactions hold unparalleled promise for building complex polycyclic scaffolds. They offer a number of synthetic shortcuts and concise pathways to complex synthetic targets. Yet, photochemistry never became a sought-after tool by synthetic chemists and its utilization in high-throughput synthesis is simply non-existent. Specifically, we aim to develop a new photoassisted synthetic methodology for rapid access to topologically diverse N,O,S-polyheterocycles, containing a large fraction of sp3 hybridized carbon atoms and stereogenic centers, and decorated by various functional groups and carbo/heterocyclic pendants rigidly or semi-rigidly held in a unique spatial configuration by these novel core frameworks with a minimal number of rotatable bonds. The synthetic strategy will involve key photochemical steps and their combination with ground state reactions, most prominently our recently discovered intramolecular cycloadditions of azaxylylenes photogenerated via excited state proton transfer from the amido or amino-group to the carbonyl group or imine. Achieving a well-defined three-dimensional relationship within an assortment of functional groups and/or heterocyclic moieties is central to synthetic medicinal chemistry. The broad objective is to generate potential pharmacophores by systematically sampling the chemical space with diversified core structures augmented with a range of peripheral functionalities. From the high throughput chemistry standpoint this task can only be achieved with a diverse set of distinctive core scaffolds suspending a variety of functional pendants in a unique 3D pattern. High throughput synthetic methods are blamed for steering discovery efforts toward achiral, aromatic compounds while natural products, possessing a broad spectrum of bioactivity, look nothing like the sp2-dominated aromatic heterocycles. Our photoassisted synthetic methodology will produce a variety of unique (poly)heterocyclic core scaffolds containing high number of saturated, i.e. sp3, carbons quantified by Lovering's Fsp3 saturation parameter.